Oxalobacter formigenes (Oxf) is a gram-negative, anaerobic bacterium that is able to metabolize dietary oxalate in the intestinal tract of humans. It is present in approximately 70% of the normal adult population. The absence of Oxf could permit higher absorption of dietary oxalate, leading to higher urinary oxalate, and thus, greater predisposition to calcium oxalate renal calculus formation. Preliminary data support this possibility; to evaluate the hypothesis more definitively, we propose a case-control study of 275 prospectively enrolled patients presenting to urologists at two Boston hospitals with recurrent episodes of calcium oxalate urolithiasis. One age and sex-matched control will be enrolled for each case, selected from among the spouses or cohabitees of other stone formers from the same hospitals. Oxf will be detected by potymerase chain reaction (PCR) testing of fecal smears, conducted on two samples for each subject. Information on factors that might affect Oxf such as consumption of oxalate and calcium-containing foods and antibiotic use, and on known risk factors for renal calculus formation, including fluid intake and personal and family history of calculi, will be obtained by telephone interview. A modified version of the food frequency questionnaire from the Nurses' Health Study will be used to obtain the dietary information. The sample size will be large enough to detect a 40% or larger reduction in the risk of calcium oxalate renal calculi among subjects who are positive for Oxf relative to those who are not. The interaction between Oxf and other risk factors will also be examined, to develop a new risk profile for the development of calcium oxalate calculi. A subset of 140 cases and 140 controls will have 24 hour urinary volume, oxalate, and other factors measured twice under their usual dietary conditions, and correlated with the presence or absence of Oxf, and its quantitative level. The sample size will be sufficient to detect, separately in men and women, a 20% difference in oxalate excretion between those who are negative for the bacterium and those who are positive. Urolithiasis is common in the U.S. population and the severe pain with which it is often associated has a substantial impact on quality of life. The condition also accounts for considerable utilization of medical care resources. The large majority of calculi are predominantly calcium oxalate. If the absence of Oxf is shown to be relevant to the etiology of oxalate stone formation, the possibility is raised for future intervention strategies which might eventually lead to a significant reduction in the recurrence of renal calculi.